The genetic basis and pathophysiology of dyskeratosis congenita V1
Research type
Research Study
Full title
The genetic basis and pathophysiology of dyskeratosis congenita and aplastic anaemia
IRAS ID
334497
Contact name
Inderjeet Dokal
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
5 years, months, days
Research summary
Dyskeratosis congenita (DC) is an inherited disorder characterized by abnormal skin pigmentation, leucoplakia (white patches), and nail abnormalities. Bone marrow failure occurs in approximately 80% of cases and is the principal cause of premature mortality. A Dyskeratosis Congenita Registry (DCR) was established by Professor Dokal in 1995 at Hammersmith Hospital to facilitate research with the long term aim of improving diagnosis and treatment. This registry moved with us to Queen Mary University of London/Barts Health in 2006. To date the DCR has facilitated studies on 460 families. This has led to the identification of several DC genes (e.g. DKC1, TERC, TERT, NOP10, RTEL1, PARN) and in turn to the development of accurate genetic testing which facilitates early diagnosis. Furthermore some of the DC genes (e.g. TERC and TERT) have been found to be mutated in a sub−group of patients with the more common idiopathic aplastic anaemia (AA) as well as myelodysplasia (MDS). The link between DC and idiopathic AA has therefore been established; DC, idiopathic AA and myelodysplasia can therefore be regarded as variants of the same bone marrow failure syndrome. We propose to undertake further research studies in order to:
1. Identify the disease genes/elements that are mutated in many (>30%) DC patients that remain uncharacterized and determine whether or not they are also mutated in patients with idiopathic AA and myelodysplasia(MDS).
2. Understand how defects/mutations in DC genes (e.g. DKC1, POT1) cause disease.
3. Undertake studies to determine whether it is possible to correct the primary defect in patient cells.
Collectively, these studies will lead to a better understanding of DC and idiopathic AA and myelodysplasia(MDS). They will also provide the basis for improving the diagnostic evaluation of these patients as well as new therapeutic approaches that are needed since conventional therapies are unsatisfactory for many patients.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
23/EM/0275
Date of REC Opinion
10 Jan 2024
REC opinion
Further Information Favourable Opinion